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1. Int J Dermatol. 2013 May;52(5):575-9. doi: 10.1111/j.1365-4632.2012.05743.x. Epub 2013 Jan 20. Stevens-Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africa: a multicentric study in four countries. Saka B, Barro-Traoré F, Atadokpédé FA, Kobangue L, Niamba PA, Adégbidi H, Yedomon HG, Traoré A, Pitché VP. Department of Dermatology, CHU Tokoin, University of Lomé, Lomé, Togo. Abstract OBJECTIVE: The purpose of this study was to document the clinical profile, etiologies, and outcomes of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in hospitals in four sub-Saharan African countries. PATIENTS AND METHODS: A retrospective study on cases of SJS/TEN treated in dermatology departments and/or intensive care units in four sub-Saharan African countries (Benin, Burkina Faso, Central African Republic, and Togo) from 2000 to 2010. The study focuses on variables such as age, sex, type of SJS/TEN, epidermal detachment of the skin surface, HIV status, drug(s) involved, and outcomes (death and sequelae). RESULTS: This study identified 177 cases of SJS/TEN from 2000 to 2010: 129 with SJS; 37 TEN; and 11 overlapping SJS/TEN. The average age of patients was 32.3 ± 15.4 years, and the sex ratio (M/F) was 0.6. HIV serology was positive in 69 (54.8%) of the 126 patients tested. Antibacterial sulfonamides (38.4%) were the most commonly used drugs followed by nevirapine (19.8%) and tuberculosis drugs (5.6%). We recorded 22 deaths (i.e. six cases of SJS, 15 of TEN, and one of overlapping SJS/TEN). Of the 22 patients who died, 16 were infected with HIV; among them, seven had an opportunistic infection (four cases of cerebral toxoplasmosis and three of pulmonary tuberculosis). Twenty-seven cases of sequelae were noted with a large part of eye complications. CONCLUSION: This study has highlighted: (i) the high proportion of patients infected with HIV among patients who had SJS/TEN in sub-Saharan Africa; (ii) the high frequency of antiretroviral drugs as new SJS/TEN causes in sub-Saharan Africa; and (iii) the impact of HIV infection on morbidity and mortality of these affections. © 2013 The International Society of Dermatology. 2. Int J Tuberc Lung Dis. 2012 Sep;16(9):1260-4. doi: 10.5588/ijtld.11.0187. Epub 2012 Jun 28. Multiple drug hypersensitivity reactions to anti-tuberculosis drugs: five cases in HIVinfected patients. Lehloenya RJ, Wallace J, Todd G, Dheda K. Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa. [email protected] Abstract BACKGROUND: The paucity of effective anti-tuberculosis drugs often justifies rechallenge with first-line drugs following adverse drug reactions (ADR) to eliminate the offending drug from the regimen. Rechallenge is usually performed under cover of drugs the patient has not been exposed to previously. The occurrence of hypersensitivity reactions to both the first-line and cover drugs poses a therapeutic dilemma and makes it difficult to identify the offending drug(s). OBJECTIVE: To characterise multiple drug hypersensitivity (MDH) in five human immunodeficiency virus (HIV) infected patients with previous tuberculosis (TB) associated ADR. DESIGN: The series is part of an ongoing randomised controlled trial assessing rechallenge dosing following TB-associated cutaneous ADR. RESULTS: The MDH was secondary to both first- and second-line anti-tuberculosis drugs. Itch, oedema, eosinophilia and fever were the most common features of MDH. Acute peripheral neuropathy associated with ethionamide, streptomycin (SM) and/or ofloxacin (OFX), to our knowledge not previously described in relation to MDH and these drugs, occurred in two patients. SM and OFX were associated with the most reactions. One patient had morphologically different reactions, namely Stevens Johnson syndrome/toxic epidermal necrolysis overlap and drug hypersensitivity syndrome, respectively to isoniazid and SM. CONCLUSION: In a description of MDH in five HIV-TB co-infected patients, including acute peripheral neuropathy, SM and OFX were the most common offending drugs. PMID: 22747953 [PubMed - indexed for MEDLINE] Related citations 3. QJM. 2012 Sep;105(9):839-46. doi: 10.1093/qjmed/hcs078. Epub 2012 Apr 28. Toxic epidermal necrolysis and StevensJohnson syndrome in South Africa: a 3-year prospective study. Kannenberg SM, Jordaan HF, Koegelenberg CF, Von Groote-Bidlingmaier F, Visser WI. Department of Medicine, University of Stellenbosch, Tygerberg, Cape Town, South Africa. [email protected] Abstract BACKGROUND: Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson syndrome (SJS) remain feared medication-related reactions. HIV infection and tuberculosis predispose to drug eruptions, yet there is a paucity of data on TEN/SJS in populations with high prevalences of both diseases. AIM: The aim of this prospective observational study was to describe the features and outcomes of patients admitted with TEN/SJS at a large academic hospital in South Africa. We aimed to identify poor prognostic indicators and to validate the use of the TEN-specific severity-ofillness score (SCORTEN) in this population. METHODS: All patients admitted with TEN/SJS over a 3-year period were enrolled. Disease severity was graded according to percentage skin involved and SCORTEN. Co-morbid diagnoses, clinical features, investigations, complications and outcomes were noted. RESULTS: 75 patients (39.9 ± 10.6 years, 16 males, 59 HIV positive) were classified as TEN (n = 42), TEN/SJS overlap (n = 11) and SJS (n = 22). Twenty-four percent died, most from refractory septic shock. Non-survivors had a higher mean SCORTEN on Days 1 and 3 (1.89 vs. 1.04, P = 0.006 and 2.27 vs. 0.90, P < 0.001). A SCORTEN ≥2 on Days 1 and 3 predicted nonsurvival (OR = 2.94, P = 0.047; OR = 7.45, P < 0.001). Other predictors of non-survival included HIV infection (OR = 6.01, P = 0.058), HIV-tuberculosis co-infection (OR = 8.5, P < 0.001), ≥40% skin involvement (OR = 20.27, P < 0.001), anaemia (OR = 4.68, P = 0.005), hypoalbuminemia (OR = 8.5, P = 0.001) and severe sepsis (OR = 71.09, P < 0.001). CONCLUSION: Most patients with TEN/SJS were HIV positive and female. We validated the use of SCORTEN and identified several prognostic indicators, most significant being HIVtuberculosis co-infection, ≥40% skin involvement and severe sepsis. PMID: 22543685 [PubMed - indexed for MEDLINE] Related citations 4. Case Rep Dermatol. 2010 Aug 9;2(2):140-145. Carbamazepine-Induced Stevens-Johnson Syndrome Sparing the Skin Previously Affected by Herpes Zoster Infection in a Patient with Systemic Lupus Erythematosus: A Reverse Isotopic Phenomenon. Tenea D. Department of Dermatology, Steve Biko Academic Hospital, University of Pretoria, Pretoria, Republic of South Africa. Abstract The reverse isotopic response is a rarely encountered phenomenon. The spared lesions are various and mainly inflammatory in nature, with herpes zoster infection being the most common. A novel case of Stevens-Johnson syndrome triggered by carbamazepine sparing the skin area previously affected by herpes zoster infection in a 39-year-old Indian female with systemic lupus erythematosus is documented. Several features as well as possible pathomechanisms that bear discussion have emerged from this case documentation. These may be related to the virus immunity, the underlying autoimmune disease (systemic lupus erythematosus) and/or drug metabolism. PMCID: PMC2978739 Free PMC Article PMID: 21076686 [PubMed] Related citations 5. Med Trop (Mars). 2010 Jun;70(3):255-8. [Stevens-Johnson syndrome and toxic epidermal necrolysis in a teaching hospital in Lomé, Togo: retrospective study of 89 cases]. [Article in French] Saka B, Kombaté K, Mouhari-Toure A, Akakpo S, Tchangaï-Walla K, Pitché P. Service de dermatologie, CHU Tokoin, Lomé, Togo. [email protected] Abstract OBJECTIVES: The purpose of this study was to document epidemiological features, outcomes, and aetiologies of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a teaching hospital in Lomé, Togo. METHOD: A retrospective study of patients with SJS/TEN treated from January 2002 to April 2009 in a teaching hospital in Lomé was conducted. RESULTS: During the study period, 89 patients were treated for SJS/TEN, i.e., SJS in 76 cases, TEN in 9, and overlapping SJS/TEN in 4. Mean age was 30.3 +/- 13.4 years and sex ratio (M/F) was 0.7. Serological testing for HIV was carried out in 75 patients and was positive in 41 (54.6%) including 36 patients with SJS, 3 with TEN and 2 with overlapping SJS/TEN. A total of 9 patients died including 4 with SJS, 4 with TEN and one with overlapping SJS/TEN. Six of the patients who died were HIV-infected. Complications included blindness in 3 cases, moderate dry eye syndrome in 1, vaginal synechiae in 2, synechiae of labial commeasures in 1, and hypertrophic scars in 1. Antibacterial sulphonamides (50.6%) were the most commonly implicated drugs followed by nevirapine (23.6%), non-steroidal anti-inflammatory drugs (5.6%), and anti-epileptic medications (3.4%). DISCUSSION: Our results also document the high frequency of nevirapine as a new SJS/TEN cause unrelated to antibacterial sulphonamides. With increasing access to HIV medication in sub-Saharan Africa countries, practitioners should take these data into account for patient monitoring. PMID: 20734593 [PubMed - indexed for MEDLINE] Related citations 6. Niger Postgrad Med J. 2010 Jun;17(2):160-3. Prevalence of cutaneous drug eruptions in adult Nigerians with HIV/AIDS. Salami TA, Asalu AF, Samuel SO. Department of Medicine, Ambrose Alli University (AAU) Ekpoma, Edo State, Nigeria. [email protected] Abstract BACKGROUND: Adverse cutaneous drug eruptions are dreaded complication of drug use and this is more so when it occurs in the setting of human immune virus (HIV) infection and acquired immune deficiency syndrome (AIDS). AIMS AND OBJECTIVES: This study aims to look at the prevalence of cutaneous drug eruptions in adult Nigerians with HIV/AIDS and find out the etiological agents, outcome, and prognosis of such occurrence in Irrua Specialist Teaching Hospital, Irrua Edo State Nigeria. SUBJECTS AND METHODS: A retrospective study of cutaneous drug eruptions in patients with HIV/AIDS managed in this centre over the past five years (between January 2001 and December 2005 prior to initiation of antiretroviral therapy) was carried out. RESULTS: A total of 900 patients with HIV/AIDS were managed during this period (antiretroviral treatment was not available during this period). Twenty five of these patients (2.8%) not had cutaneous drug eruptions (2.8%). Erythema multiforme major or Steven Johnson Syndrome (SJS)-40% and Toxic epidermal necrolysis (TEN)-20% were the most frequent types of adverse cutaneous drug events found while combination antituberculosis agent of Isoniazid/Thiacethazone (64%) and anti malarial Sulphadoxine/Pyrimethamine (20%) were the notable culprit drugs found to be responsible for these. There was a 20% fatality rate. CONCLUSIONS: Treatment of tuberculosis which is the most common AIDS presenting illness with anti tuberculosis regimen that includes thiacethazone and the ready availability of anti malarials over the counter without prescription are responsible for the findings of this study. Avoiding drugs such as those found to be culprit agents in this study in patients with HIV/AIDS; right prescription practice by health practitioners as well as more intense health education of the public on the hazards of self prescription will all go a long way in minimising the occurrence of these events. PMID: 20539333 [PubMed - indexed for MEDLINE] Related citations 7. Dermatol Clin. 2006 Oct;24(4):459-72, vi. Adverse cutaneous drug eruptions and HIV: a clinician's global perspective. Todd G. Division of Dermatology, University of Cape Town, Faculty of Health Sciences, Nard 623, Cape Town, South Africa. [email protected] Abstract Adverse drug reactions (ADRs) are common and mostly avoidable. Some ADRs cannot as yet be predicted, but at-risk populations/patients and high-risk drugs are identifiable. HIV-infected patients are at risk of developing cutaneous ADRs, especially Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug hypersensitivity syndrome. Multiple factors of causation variably present in patients with HIV infection best explain the pathogenesis of these cutaneous ADRs. When no effective alternate therapy is available, drug rechallenge in HIVinfected patients can be attempted with little morbidity or mortality if done according to rationalized protocols. PMID: 17010776 [PubMed - indexed for MEDLINE] Related citations 8. Med Trop (Mars). 2005 Sep;65(4):359-62. [Stevens-Johnson syndrome and toxic epidermal necrolysis after intake of rifampicin-isoniazid: report of 8 cases in HIV-infected patients in Togo]. [Article in French] Pitche P, Mouzou T, Padonou C, Tchangai-Walla K. Service de Dermatologie, CHU-Tokoin, Lomé, Togo. [email protected] Abstract Dermatological reactions are frequent drug-related complications in patients with HIV infection. The most serious disorders are Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), a.k.a. Lyell's syndrome, that are potentially fatal. The purpose of this report is to describe 8 cases of SJS/TEN observed in Lomé teaching hospital (Togo) after intake of a combination of rifampicin-isoniazid by HIV-infected patients. There were 5 men and 3 women with a mean age of 28 years. All patients presented AIDS. The disorder was SJS in 3 cases and TEN in 5. In 6 cases, manifestations occurred during initiation of treatment (mean delay for onset, 16 days). In the remaining two cases, manifestations occurred 6 days and 8 days respectively after beginning treatment for recurrent tuberculosis. Mean skin detachment was 8% in patients with SJS and 55.7% in patients with TEN. Five patients including 4 with TEN and 1 with SJS died. This study documents incrimination of combined rifampin-isoniazid treatment in the occurrence of SJS/TEN in patients with HIV infection and confirms the severity and poor prognosis of these disorders. The presence of opportunistic infections such as pulmonary tuberculosis may be an unfavourable prognostic factor in immunocompromised patients with these severe dermatological disorders. PMID: 16548490 [PubMed - indexed for MEDLINE] Related citations 9. East Afr Med J. 1991 Jan;68(1):64-6. Stevens-Johnson syndrome during antituberculosis chemotherapy in HIV- seropositive patients: report on six cases. Wirima JJ, Harries AD. Department of Medicine, Kamuzu Central Hospital, Lilongwe, Malawi. Abstract Hypersensitivity reactions may occur during antituberculous chemotherapy. Severe reactions are rare, and in the three years 1983-86 during which we have both worked in Africa managing large numbers of patients with tuberculosis we only saw one or two cases with severe and generalised cutaneous hypersensitivity. In the last 12 months, however, there have been a number of cases with severe Stevens-Johnson syndrome which developed during antituberculous chemotherapy and has invariably been associated with seropositivity to HIV (human immunodeficiency virus). PIP: Severe cutaneous hypersensitivity historically has been an extremely rare complication of antituberculous chemotherapy in African patients. However, the authors have observed 6 such cases in the past year alone in Malawi. In 5 of these cases, patients with sputum-negative pulmonary tuberculosis who were treated with streptomycin, isoniazid, and thiacetazone developed severe Stevens-Johnson syndrome in association with high fever in the third or fourth week of chemotherapy. The 6th patient with Stevens-Johnson syndrome in association with high fever in the third or fourth week of chemotherapy. The 6th patient with StevensJohnson syndrome was diagnosed with tuberculous pleural effusion. All 6 patients had concomitant human immunodeficiency virus (HIV) infection. It is unknown how HIV infection apparently promotes severe cutaneous side effects in antituberculous chemotherapy recipients. Thiacetazone is considered to be the agency responsible for this side effect, and use of the more expensive streptomycin, rifampicin, isoniazid, and pyrazinamide regimen is recommended. Given the association between HIV infection and a hypersensitivity reaction, all patients who developed Stevens-Johnson syndrome should be screened for HIV. PMID: 2060484 [PubMed - indexed for MEDLINE] Related citations 10. J Am Acad Dermatol. 1988 Sep;19(3):451-7. Cutaneous manifestations of human immunodeficiency virus in Lusaka, Zambia. Hira SK, Wadhawan D, Kamanga J, Kavindele D, Macuacua R, Patil PS, Ansary MA, Macher AM, Perine PL. University Teaching Hospital, Lusaka, Zambia. Abstract Of the 1124 human immunodeficiency virus (HIV)-infected patients studied, one or more cutaneous lesions were found in 113 (98.3%) of the 115 patients with acquired immunodeficiency syndrome (AIDS) and in 541 (53.6%) of 1009 patients with AIDS-related complex (ARC). Kaposi's sarcoma, multidermatomal, necrotic herpes zoster, and pruritic maculopapular rashes are common cutaneous manifestations of AIDS and its related complex (ARC) in Zambia. The maculopapular rash results from a lymphoplasmacytic angiitis in the dermis, possibly in response to the presence of HIV in the dermis. Candidiasis, severe genital herpes, extensive molluscum contagiosum, and tinea corporis were less frequent and usually refractory to treatment. Drug reactions are also frequent in Zambians with AIDS. In seven patients given streptomycin, thiacetazone, and rifampicin for treatment of pulmonary tuberculosis, Stevens-Johnson syndrome occurred shortly after therapy was begun, and two died despite high-dose prednisone and discontinuance of tuberculosis therapy. Extensive seborrheic dermatitis refractory to topical fluorinated corticosteroids is also an associated condition in AIDS patients who have pulmonary tuberculosis. PIP: Cutaneous manifestations of AIDS and AIDS-related complex were studied in a population of 1124 HIV seropositive patients at a hospital in Lusaka, Zambia. 115 of the patients had AIDS, and 1009 had AIDS-related complex. Drug eruptions occurred in 22 patients; 2 died of Stevens-Johnson syndrome subsequent to drug therapy for tuberculosis. The most frequently seen cutaneous manifestations were candidiasis, Kaposi's sarcoma, herpes zoster, seborrheic dermatitis, herpes genitalis, and papular dermatoses. The pruritic maculopapular eruption occurred in crops, healed, and recurred. It was one of the most unique dermatologic manifestations of AIDS found in Africa. Seborrheic dermatitis occurred frequently in patients who also had pulmonary tuberculosis. PMID: 2971691 [PubMed - indexed for MEDLINE] Related citations 11. Trop Geogr Med. 1980 Sep;32(3):224-6. Stevens-Johnson's syndrome in Africans. Enu CC, Elegbeleye OO, Femi-Pearse D. Abstract Three cases of Stevens-Johnson's syndrome seen at the Lagos University Teaching Hospital are reported. The clinical features did not differ from those described in temperature countries. Steroid therapy and intravenous infusion still form the major part of the management in this life-threatening condition. PMID: 7210156 [PubMed - indexed for MEDLINE] Related citations 12. Am J Trop Med Hyg. 2006 May;74(5):738-43. Severe cutaneous reactions to sulfadoxinepyrimethamine and trimethoprimsulfamethoxazole in Blantyre District, Malawi. Gimnig JE, MacArthur JR, M'bang'ombe M, Kramer MH, Chizani N, Stern RS, Mkandala C, Newman RD, Steketee RW, Campbell CH. Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. [email protected] Abstract We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprimsulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible. Free Article PMID: 16687672 [PubMed - indexed for MEDLINE] Related citations